Department of Urology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Clin Cancer Res. 2012 Aug 1;18(15):4163-72. doi: 10.1158/1078-0432.CCR-11-2449. Epub 2012 Jun 13.
We aimed to analyze whether ERG rearrangement in biopsies could be used to assess subsequent cancer diagnosis in high-grade prostatic intraepithelial neoplasia (HGPIN) and the risk of lymph node metastasis in early prostate cancer.
Samples from 523 patients (361 with early prostate cancer and 162 with HGPIN) were collected prospectively. On the basis of the cutoff value established previously, the 162 patients with HGPIN were stratified to two groups: one with an ERG rearrangements rate ≥1.6% (n = 59) and the other with an ERG rearrangements rate <1.6% (n = 103). For the 361 prostate cancer cases undergoing radical prostatectomy, 143 had pelvic lymph node dissection (node-positive, n = 56 and node-negative, n = 87). All ERG rearrangement FISH data were validated with ERG immunohistochemistry.
A total of 56 (of 59, 94.9%) HGPIN cases with an ERG rearrangements rate ≥1.6% and 5 (of 103, 4.9%) HGPIN cases with an ERG rearrangements rate <1.6% were diagnosed with prostate cancer during repeat biopsy follow-ups (P < 0.001). There were significant differences in ERG rearrangement rates between lymph node-positive and -negative prostate cancer (P < 0.001). The optimal cutoff value to predict lymph node metastasis by ERG rearrangement was established, being 2.6% with a sensitivity at 80.4% [95% confidence interval (CI), 67.6-89.8] and a specificity at 85.1% (95% CI, 75.8-91.8). ERG protein expression by immunohistochemistry was highly concordant with ERG rearrangement by FISH.
The presence of ERG rearrangement in HGPIN lesions detected on initial biopsy warrants repeat biopsies and measuring ERG rearrangement could be used for assessing the risk of lymph node metastasis in early prostate cancer.
我们旨在分析活检中 ERG 重排是否可用于评估高级别前列腺上皮内瘤变(HGPIN)中后续癌症诊断以及早期前列腺癌中的淋巴结转移风险。
前瞻性收集了 523 例患者(361 例早期前列腺癌和 162 例 HGPIN)的样本。基于先前建立的截止值,将 162 例 HGPIN 患者分为两组:一组 ERG 重排率≥1.6%(n=59),另一组 ERG 重排率<1.6%(n=103)。对 361 例接受根治性前列腺切除术的前列腺癌病例,其中 143 例进行了盆腔淋巴结清扫术(淋巴结阳性,n=56,淋巴结阴性,n=87)。所有 ERG 重排 FISH 数据均通过 ERG 免疫组化进行验证。
在接受重复活检随访的患者中,59 例 ERG 重排率≥1.6%的 HGPIN 病例中,有 56 例(56/59,94.9%)和 103 例 ERG 重排率<1.6%的 HGPIN 病例中,有 5 例(5/103,4.9%)被诊断为前列腺癌(P<0.001)。淋巴结阳性和阴性前列腺癌之间的 ERG 重排率存在显著差异(P<0.001)。通过 ERG 重排预测淋巴结转移的最佳截止值为 2.6%,其敏感性为 80.4%(95%置信区间,67.6-89.8),特异性为 85.1%(95%置信区间,75.8-91.8)。免疫组化法检测到的 ERG 蛋白表达与 FISH 法检测到的 ERG 重排高度一致。
在初始活检中检测到的 HGPIN 病变中存在 ERG 重排提示需要进行重复活检,并且测量 ERG 重排可用于评估早期前列腺癌中的淋巴结转移风险。